Creating structural manifolds from a common precursor: basicity gradient-driven isomerization of halopyridines

5-Chloro-2,3-difluoropyridine, an intermediate in the manufg. process of an industrial pesticide, can be hydrolyzed to 5-chloro-3-fluoro-2H-pyridinone and the latter converted into 2,5-dichloro-3-fluoropyridine, 2-bromo-5-chloro-3-fluoropyridine, 5-chloro-3-fluoro-2-iodopyridine and 3-chloro-5-fluoropyridine. Consecutive treatment of these four substrates with lithium diisopropylamide and carbon dioxide or lithium diisopropylamide and iodine affords the corresponding 4-pyridinecarboxylic acids and 4-iodopyridines, resp. Amide-promoted deprotonation of such 4-iodopyridines triggers an isomerization in which lithium and iodine change places. The resulting species can be trapped with carbon dioxide to give the acids I (X = Cl, Br, I) or neutralized to give the halopyridines II. The iodopyridines II (X = Cl, Br) can be converted into the acids III, the latter product leading also to the congeners III (X = I, H). The diiodopyridine II (X = I) provides an entry to the halopyridine II (X = H), which at the same time may act as the precursor to 3-chloro-5-fluoro-2,6-diiodo-4-pyridinecarboxylic acid, 5-chloro-3-fluoro-6-iodo-2-pyridinecarboxyic acid or 3-chloro-5-fluoro-2,6-pyridinecarboxylic acid. Finally, 5-chloro-3-fluoro-2-pyridinecarboxylic acid is accessible from either 2-bromo-5-chloro-3-fluoropyridine or 5-chloro-3-fluoro-2-iodopyridineone. [on SciFinder (R)]